Non-digestible sugar-coated products and process

ABSTRACT

A method and composition are provided for coating a component to achieve colon-targeted delivery. A component is coated with a fructose-based non-digestible carbohydrate such as a inulin, fructo-oligosaccharide or neosugar. The coated component is orally administered to a monogastric animal. The non-digestible coating causes the composition to pass through the stomach and small intestine without being degraded, and delivers the component to the colon where the coating is digested by microbial fermentation and the component is released.

This application is a continuation of U.S. application Ser. No.13/090,077, filed Apr. 19, 2011, which is a continuation of U.S.application Ser. No. 12/362,858, filed Jan. 30, 2009, which is acontinuation of U.S. application Ser. No. 10/686,129, filed Oct. 14,2003, which is a continuation of international application numberPCT/US02/12323, filed Apr. 17, 2002, which claims priority to U.S.provisional application No. 60/284,389, filed Apr. 17, 2001. Thecontents of these applications are incorporated herein in theirentirety.

BACKGROUND

1. Field of the Invention

This invention is directed to methods and compositions forcolon-targeted delivery of components.

2. Description of the Prior Art

Fructan is a non-structural carbohydrate and is a polymer of fructose.Fructans have a general structure of a glucose linked to multiplefructose units. There are several types of fructans present in nature,and they can broadly be divided into 3 groups: inulins,fructo-oligosaccharides (FOS), and neosugars.

Inulin is a polydisperse fructan extracted from plants, includingchicory root, asparagus shoot, banana, dandelion, garlic, globeartichoke, Jerusalem artichoke, leek, onion, rye, salsify, and wheat,that has not been digested enzymatically by inulinase. The chemicalstructure of inulin is shown in FIG. 1. GF_(n) is a glucose endingfructan chain, and n represents chain length. Inulin has a degree ofpolymerization (DP) in the approximate range of 2 to 60 units of β(2-1)fructose with a glucosyl terminus. The average DP is greater than 10units.

Fructo-oligosaccharide (FOS) is partially hydrolyzed inulin with a DP inthe approximate range of 2 to 20 units of β(2-1) fructose with either aglucosyl or a fructosyl terminus. The average DP is less than 10 units.Chemical structures of glucose ending fructan chains (GF_(n)) andfructose ending chains (F_(n)) are shown in FIGS. 2A and 2B. Inulin ishydrolyzed with inulinase, for example, to producefructo-oligosaccharides.

Neosugars are fructo-oligosaccharides that can be prepared, for example,by an enzymatic reaction using sucrose and the enzymefructosyltransferase from an organism such as Aspergillus niger. Thechemical structure of neosugar is shown in FIG. 3. Neosugars have DP inthe approximate range of 2 to 4 units of β(2-1) fructose with a glucosylterminus. The average DP is about 2 to 3 units. Collectively, inulin,FOS, and neosguars are referred to herein as fructans.

Fructans are currently used as an animal feed supplement, mixed with theanimal feed. Fructans are found in the feed of monogastric animals,including poultry, turkey, swine, dog, cat, horse, and bovine calfdiets. (Bovine calves begin their development as monogastric mammals).Fructans are also added to food and drink for human consumption. As anoral supplement, fructans have been shown to improve weight gain, reducefecal odor, reduce colon cancer, lower blood triglycerides, increasemineral uptake, and promote a healthy gastrointestinal system.

Fructans are essentially “non-digestible” by monogastrics; they are notdigested in the stomach or small intestines. Consequently, thefructan-coated components of the instant invention are not digested inthe stomach of monogastric mammals and pass directly to the colon wherethe fructan is fermented by organisms residing in the colon. Asfructan-fermenting bacteria grow, there is a concomitant decrease in theconcentrations of putrefactive bacteria such as Escherichia coli,Clostridium perfringens and Salmonella, which are widely known toproduce malodorous aromatic metabolites. Bacteria that utilize fructansas a source of energy include beneficial bacteria in the genus ofBifidobacterium and Lactobacillus. Non-digestible ingredients, such asfructans, that beneficially affect the host by selectively stimulatingthe growth and/or activity of bacteria in the colon that can improvehost health and known as “prebiotics”.

Wang et al. (Journal of Applied Bacteriology, 75:373-380, 1993) lookedat mixed populations of colonic bacteria in a batch culture grown oninulin, fructo-oligosaccharide, polydextrose and starch. The type ofcarbohydrate used in each batch culture had no effect on total aerobic,anaerobic or Bacteriodes counts. Bifidobacteria counts were 5 to 13times higher with batch cultures grown on fructo-oligosaccharide andinulin then polydextrose and starch. The coliform counts were 8 to 630times lower with batch cultures grown on inulin andfructo-oligosaccharide than polydextrose and starch. Lactobacilluscounts were 316-1,000 times lower in batch cultures when inulin was usedas a substrate than fructo-oligosaccharide, starch and polydextrose.

In order for inulin and fructo-oligosaccharides to affect the microbialpopulation in the colon, they must first pass through the stomach andsmall intestine. Samples taken from the ileum of humans receiving dietscontaining inulin or fructo-oligosaccharides have been shown to exhibitan 89% and 88% recovery respectfully (Ellegard et al., European Journalof Clinical Nutrition, 51:1-5, 1997). Similarly, humans receivingNeosugar in their diet have been shown to exhibit an 89% recovery inileal samples taken (Molis et al., American Journal of ClinicalNutrition, 64:324-328, 1996). The fraction of fructan that is notrecovered is digested in the gastrointestinal tract and then absorbed asglucose or fructose. The digestion may have occurred in the ileum viabacterial fermentation or by acid digestion in the stomach (Simon etal., Gastroenterology, 86:174-193, 1984). In vitro studies have shownthat fructans and inulin are hydrolyzed at a low rate and a very low pH(Nilsson et al., Journal of Nutrition, 86:1482-1486, 1988).

Once the fructans reach the colon, they are fermented completely by themicrobial flora. (Jenkins et al., Journal of Nutrition, 129:1431S-1433S,1999). With fermentation of the fructans in the colon, changes occur tothe microbial flora. Most notably, the Bifidobacteria sp., has beenshown to increase 5 to 63 fold (Djouzi et al., British Journal ofNutrition, 78:313-324, 1997). A review by Loo et al. (British Journal ofNutrition, 81:121-132, 1999) of ten trials studying the increase inBifidobacteria sp. in the colon of humans receiving inulin orfructo-oligosaccharide in their diets showed a statistically significantincrease in Bifidobacteria sp. The average for the nine trials was an11.8-fold increase in Bifidobacteria sp. with a high of a 22-foldincrease. Other changes that were observed in colonic populations ofhumans receiving inulin and fructo-oligosaccharide include thesignificant decrease in Bacteriodes sp. and/or Clostridia sp. (Gibson etal., Journal of Nutrition, 125:1401-1412, 1995; Kleessen et al.,American Journal of Clinical Nutrition, 65:1397-1402, 1997).

The increase of Bifidobacteria has been shown to be correlated to a doseresponse to fructan addition to the diet. Studies have shown that humanssubjects exhibit no increase in Bifidobacteria sp. until their dietcontains 10 grams of Neosugar per day (Bouhnik et al., Journal ofNutrition, 129:113-116, 1999). A review by Roberfroid et al. (Journal ofNutrition, 128:11-19, 1998) combined data for inulin,fructo-oligosaccharide and Neosugar and concluded that log increases incounts do not correlate to daily doses administered. One variableconsidered to correlate with increases was the initial number ofBifidobacteria in the feces. It appeared that the lower the initialnumber, the greater the increase whatever the dose, within the range of4 to 20 or more grams per day. Consuming a few grams of any of thesefructans daily could be sufficient to cause a significant increase incolonic Bifidobacteria.

SUMMARY OF THE INVENTION

According to one embodiment of the present invention, a method andcomposition are disclosed for coating a component to achievecolon-directed delivery. The invention includes coating a component witha non-digestible composition, such as a fructan, to produce a feedsupplement. The coated component, a non-digestible coated composition,is administered to a monogastric animal, where the non-digestible coatedcomposition passes through the stomach and small intestine without beingdegraded, and is delivered to the colon where the coating is digestedand the component is released.

According to a preferred embodiment of the present invention, theindigestible coating is fructan.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the chemical structure of inulin.

FIGS. 2A and 2B show chemical structures of fructo-oligosaccharides.

FIG. 3 shows the chemical structure of neosugar.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is directed to a method and composition forcoating a component for delivery targeted to the colon of an animal. Itis often desirable to deliver components, such as drugs, vitamins,minerals, metabolites, beneficial bacteria, and other molecules, to thecolon of an animal without subjecting the component to the acids anddigestive enzymes of the stomach and small intestine.

Administration by conventional means, including oral, intravenous,percutaneous, or other known delivery methods, generally results inreduced bioavailability of the component. Degradation or alteration ofthe component by digestive enzymes and/or low pH may occur in thestomach and small intestine when conventional oral preparations areused, reducing or inactivating the therapeutic activity of thecomponent.

Intravenous and percutaneous administration generally requires a largedosage, sufficient to ensure that the desired level of the componentreaches the colon. Such routes of administration are generally notsuitable for components such as beneficial bacteria and many vitamins,minerals and metabolites.

Drugs can be targeted to the colon by coating the drug formulations withpolymeric coatings, such as acrylic acid derivatives or cellulosederivatives, that can withstand both low and slightly basic pH valuesfor several hours. A disadvantage of this targeting method is theuncertainty of location and environment in which the polymeric coatingwill be degraded. The delay in coating degradation is based on theamount of time spent in a particular pH environment. If the coated drugis delayed in the upper gastrointestinal tract, such as for mechanicalreasons, the drug may be released in a non-target location, such as thesmall intestine.

The present invention provides a safe and effective method andcomposition for targeting components specifically to the colon based onthe presence or absence of bacteria that degrade a prebiotic, such asfructan. The components to be administered are coated with a prebioticthat is not digested in the stomach or small intestine, but that isdegraded by bacteria present in the colon, especially of monogastricanimals.

As used herein, “prebiotic” is intended to mean a non-digestible foodingredient that beneficially affects the host by selectively stimulatingthe growth and/or activity of one or a limited number of bacteria in thecolon, that can improve host health. Oligosaccharides such as inulin,fructo-oligosaccharide and neosugar, which cannot be digested exceptthrough bacterial activity, are considered prebiotics. Many othercarbohydrates can be considered prebiotics, for example, those listed inTable 1. Other ingredients that reach the colon undigested and can beconsidered prebiotics include peptides, proteins, and lipids. Criteriafor classifying a substance as a prebiotic may include:

-   -   1. Not hydrolyzed or absorbed in the upper part of the        gastro-intestinal tract.    -   2. Selectively fermented by potentially beneficial bacteria in        the colon.    -   3. Alters the composition of the colonic microbial flora towards        a healthier composition.    -   4. Preferably, induces effects that are beneficial to the host        health.

TABLE 1 Candidate Prebiotic Carbohydrates Oligosaccharide ChemicalComposition Fructo-oligosaccharide β(2-1) fructan with degrees ofpolymerization ranging from 2-20 units and has an average degrees ofpolymerization of 2 to 10 Inulin β(2-1) fructan with degrees ofpolymerization ranging from 2-60 units and has an average degrees ofpolymerization greater than 10 Neosugar β(2-1) fructan with degrees ofpolymerization ranging from 2-4 units and has an average degrees ofpolymerization from about 2 to about 3 Polydextrins Complex mixture ofglucose-containing Oligosaccharide Transgalactosylated Mainly6′galactosyllactose, DP of oligosaccharides oligosaccharide fraction 2-5(primarily DP 3); 55% pure Galacto- Oligogalactose (85%), small amountsof glucose, oligosaccharides galactose, and lactose Soya Stachyose(fructose, galactose, galactose, oligosaccharides glucose) and raffinose(fructose, galactose, glucose), DP 3-4 Xylo- B(1-4) linked xylose; 70%pure, DP of oligosaccharides oligosaccharide fraction is 2-4 Isomalto-Mixture of α(1-6) linked glucose oligomers oligosaccharides (isomaltose,panose, isomaltotriose) Lactulose Galactose and fructose-containingdisaccharide DP = Degrees of polymerization

Many bacteria can utilize fructans for growth. These include lactic acidbacteria, such as Lactobacillus sp. and Bifidobacterium sp., which areconsidered probiotics. Many bacteria, such as, Escherichia coli andSalmonella sp. cannot utilize fructans for growth.

As used herein, “non-digestible” is intended to mean that a substancetaken orally is substantially resistant to chemical and enzymaticdegradation in the stomach and small intestine, but is susceptible todegradation in the colon.

As used herein, “monogastric” is intended to encompass any animal havingone stomach. Examples of monogastric animals include, but are notlimited to, horses, emu, ostrich, dog, cat, swine, bear, turkey,chickens, ducks, quail, pheasants, reptiles, and humans. Pre-ruminantanimals such as young cattle, buffalo, bison, and elk are alsoencompassed by the term monogastric as these animals are bornmonogastric and then develop into true ruminants as adults.

Additionally, the compositions and methods of the present invention aresuitable for any animal that breaks down fructose-based oligosaccharideselectively in a specific part of the gastrointestinal tract. Breakdownof a fructose-based oligosaccharide generally requires the presence ofbacteria capable of fermenting the oligosaccharides, such as those fromthe genus Bifidobacterium and Lactobacillus. The compositions of theinvention can be selectively delivered to the colon by administration ofthe coated composition to any animal having fructan-fermenting bacteriapresent in at least part of their digestive tract. For those animalshaving insufficient Fructan-fermenting bacteria in their digestivetract, Fructan digesting bacteria can be optionally added along with thediet.

As used herein, “component” is intended to encompass any compound,molecule composition, or organism that is to be coated and delivered tothe colon in the method of the invention. Examples include, but are notlimited to, minerals, vitamins, drugs, bacteria, yeast, immunestimulators, nutrients, nutraceuticals, electrolytes, chelated minerals,molds, enzymes, energy-providing compounds, antibodies, and acids.

Minerals for colon-targeted delivery include, but are not limited to,calcium, chromium, cobalt, copper, iodine, iron, magnesium, manganese,organic trace minerals, phosphorus, potassium, selenium, sodium, sulfur,zinc, and the like. Vitamins include, but are not limited to, vitaminsA, B12, C, D, E, K, betaine, biotin, choline, folic acid, inositol,niacin, pantothenic acid, pyridoxine, riboflavin, thiamine, etc. Drugsinclude, but are not limited to, antibiotics, anti-viral agents,anti-mold agents, bloat preventatives, coccidiostat, growth enhancers,vaccines, wormers, chemotherapy agents, antitumor agents, insulin, etc.Examples of suitable drugs include Aureomycin®90 (Chlortetracyclinehydrochloride), Aureomix®500 (Chlortetracycline Hydrochloride,Penicillin G and Procaine Granule), BMD®60 (Bacitracin methylenediscalicylate), ChlorMax®-SP 500 (Chlortetracycline), Denagard®10(Tiamulin powder),Lincomix®50 (Lincomycin hydrochloride), Mecadox®10(Carbadox powder), Neo-Terramycin®50/50 (Carbadox powder), Pulmotil®90(Tilmicosin phosphate granule), Tylan®100 (Tylosin injection), and3-Nitro®20(Roxarsone).

Bacteria to be introduced into the colon include any beneficialbacteria, including, but not limited to, Bacillus coagulans, Bacilluslentus, Bacillus licheniformis, Bacillus pumilus, Bacillus subtilis,Bacteroides amylophilus, Bacteroides capillosus, Bacteroides ruminocola,Bacteroides suis, Bifidobacterium adolescentis, Bifidobacteriumanimalis, Bifidobacterium bifidum, Bifidobacterium infantis,Bifidobacterium longum, Bifidobacterium thermophilum, Entercoccuscremoris, Entercoccus diacetilactis, Entercoccus faecium, Entercoccusintermedius, Entercoccus lactis, Entercoccus thermophilus, Lactobacillusacidophilus, Lactobacillus brevis, Lactobacillus bulgaricus,Lactobacillus casei, Lactobacillus cellobiosus, Lactobacillus curvatus,Lactobacillus delbruekii, Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillusreuteri, Leuconostoc mesenteroides, Pediococcus acidilactici,Pediococcus cerevisiae, Pediococcus pentosaceus, Pripionibacteriumfreudenreichii, Propionibacterium sherimanii, Streptococcus cremoris,Streptococcus diacetilactis, Streptococcus faecium, Streptococcusintermedius, Streptococcus lactis, and Streptococcus thermophilus.

Yeast include, but are not limited to, Saccharomyces sp. and Candidasp., more specifically Saccharomyces cerevisiae and Candida utilis.Immune stimulators include, but not limited to, mannose-oligosaccharideand beta-glucan. Nutrients include, but are not limited to, amino acidssuch as arginine, glycine, lysine, methionine, taurine, threonine andtryptophan, peptides such as insulin, proteins, carbohydrates, aminoacids, bone meal, grains, egg, fats and oils, feather meal, fish meal,plant and animal byproducts, plasma, poultry byproducts, whey, and thelike.

Nutraceuticals include, but are not limited to, spices, essential oils,soy products and natural extractives such as alfalfa, angelica, anise,basil, bay leaf, calendula, camomile, caraway, cardamom, carrot, cayennepepper, chicory, celery seed, chives, cinnamon, cloves, coriander,cumin, dandelion, dill, fennel, fenugreek, garlic, glycyrrhiza, habaneropepper, horehound, horsemint, horseradish, hyssop, gentian, ginger,ginseng, juniper, kava, lemon balm, lemon grass, licorice, marjoram,melissa, mustard, netmeg, nettle, onion, oregano, parsley, pepper,peppermint, raspberry, rosemary, rue, savory, spearmint, tarragon,thyme, and vanilla.

Nutraceuticals also include, but are not limited to, herbs such asBoneset or Feverwort (Eupatorium perfoliatum), Burdock (Arctium lappa),Coltsfoot (Tussilago farfara), Comfrey (Symphytum officinale), Devil'sClaw Root (Harpagophytum procumbens), Ginkgo (Ginkgo biloba), Golden Rod(Solidago virgaurea), pot Marigold (Calencula officinalis), Meadowsweet(Filipendula ulmaria), Monk's Pepper or Chasteberry (Vitexagnus-castus), Nettle (Urtica dioicea), Red Poppy Seed (Papaver rhoeas),Raspberry leaves (Rubidus idaeus), Valerian root (Valerianaofficinalis), Vervain (Verbena officinalis), and Yellow Dock (Rumexcrispus).

Electrolytes include, but are not limited to, potassium, magnesium, andcalcium. Chelated minerals include, but are not limited to, copper,zinc, iron, manganese, chromium and magnesium bound to a protein orcarbohydrate source. Examples include, but are not limited to, Alfamin®from RK Marketing Enterprises, Inc. (Waconia, Minn.) and SQM from QualiTech Inc. (Chaska, Minn.). Other companies that produce chelatedminerals include Albion Laboratories, Inc. (Clearfield, Utah), ZinproCorporation (Eden Prairie, Minn.) and Chelated Minerals (Ogden, Utah).Molds include, but are not limited to, Aspergillus niger and Aspergillusoryzae. Enzymes include, but are not limited to, cellulase,hemicellulase, anylase, phytase, and ligninase. Energy-providingcompounds include, but are not limited to, sugars such as glucose,sucrose, fructose, propylene glycol and glucose precursors.

Antibodies include, but are not limited to, those reactive with specificbacteria and viruses and those reactive with broad classes of bacteriaand viruses. Acids include, but are not limited to, citric acid, lacticacid, and acetic acid. Additionally, other components, includingemulsifiers and surfactants, acidifiers, buffers, dietary fiber,flavoring agents, attractants, flow and anti-caking agents, grit, kelpmeal, algae, molasses, pigments, preservatives, antioxidants moldinhibitors, sweeteners, urea, yucca products, and other components, canbe coated by the method of the invention for colon-targeted delivery.

In another embodiment of the present invention, the fructan coating isused to mask or cover-up an otherwise unpalatable component. Examples ofunpalatable components include, but are not limited to, ammoniumchloride, calcium sulphate, magnesium chloride, propylene glycol, drugs,vitamins, and other ingestible compositions. In this instance, theFructan coating is provided to provide a more organoleptic composition.

In a further embodiment of the present invention, the fructan coating isused to prevent or minimize the release of components that may bedisruptive or harmful to the stomach or small intestine. For example,chemotherapy and anti-tumor agents directed to a tumor in the colon maycause undesirable effects if released in the upper gastrointestinaltract.

The coating of the present invention can also be used to improve theflowing characteristics of a component. This is especially beneficialfor components that are sticky, powdery, viscous, etc. in their uncoatedstate.

The coating can be applied by conventional methods, includingfreeze-drying, spray-coating, mixing, agglomeration, and combining arapid centrifugal application of liquid and powder to create a thin filmpolymer coating using a rotary disc type liquid/powder applicator.

In one embodiment, the component to be delivered to the colon is coatedwith fructan using a rotary driven disc system. The component can be inthe form of pellets, tablets, pieces, nuggets, crumbles, and the like,that may be of any size, and may be regular or irregular in shape. Thepellets may be, for example, in the approximate size range of 10 micronsto 100 microns in diameter. In this system, the pellets are dropped onthe disc as it rotates. This rotation carries the pellet out to thechamber wall by centrifugal force. As the pellet is turned by mixingblades mounted on the chamber walls, powdered fructan and liquid or amixture of the fructan and liquid are introduced into the chamber.Liquid, such as water or a mixture of water and fructan, is atomized bythe high-speed disc into ultra-fine particles that are applied to thepellets. The process results in a thin film coating of the carbohydrateon the component pellets.

Probiotic bacteria such as Lactobacillus sp. and Bifidobacteria sp. areknown for their ability to ferment fructans while Escherichia coli andSalmonella sp. cannot. In the colon, this positive change in themicrobial population leads to a healthier intestinal tract whichimproves immune response, weight gain, feed efficiency, nitrogenretention, mineral absorption and increased short-chain fatty acidsproduction. Other positive benefits include reduced colonization of theintestinal tract by enteric bacteria, reduced diarrhea, reduced stomachupsets, firmer feces and an increased energy source for hyperglycemicanimals such as dogs, cats and veal calves.

The chain length of the fructan is fermented differently by differentspecies of probiotic bacteria. The longer DP fructan is fermented halfas fast as fructans with shorter DP. A coating composition having alonger chain length such as inulin may be well suited for a positiveprebiotic effect throughout the colon. Fructo-oligosaccharide andNeosugar are considered a shorter DP fructans, and may be well suitedfor quick delivery to the colon. Combinations can produce a variety ofdegradation effects, as desired.

Pure cultures of different species of Bifidobacteria have been shown tohave different growth rates when grown on fructo-oligosaccharide. Inother studies mixed cultures of Bifidobacterium infantis, Escherichiacoli and Clostridium perfringens grown on fructo-oligosaccharide haveshown an inhibitory effect towards Escherichia coli and Clostridiumperfringens.

The favorable effects of soluble fiber for diabetes mellitus may also befavorable for veal calves. Veal calves in late fatting periods oftendevelop hyperglycemia, glucosuria, and insulin resistance with highlactose intakes. Kaufhold et al. (Journal of Veterinary Medicine47(1):17-29, 2000) has reported higher weight gains in veal calvesreceiving fructo-oligosaccharide. The study also showed calves receivingfructo-oligosaccharide had a lower post-prandially increase in glucoseand higher insulin concentrations. They concluded thatfructo-oligosaccharide has similar endocrine traits in veal calves as inhumans with diabetes mellitus. Mul (“Application of Oligosaccharides inAnimal Feeds”, in Proceedings: International Symposium on Non DigestibleOligosaccharides: Health Food for the Colon?, Wagneningen, Netherlands,1997) reported on field trials by Trouw Nutrition from 1990-1992 withveal calves. The majority of the field trials showed improved weightgain (0.8-2.4 kg), improved feed efficiency (3-14%), reduction indiarrhea incidence, and on average firmer feces. In one reported trial,higher weight gains were observed when a probiotic was used incombination with fructo-oligosaccharide.

The amount of the component to be administered will vary depending onthe desired effect to be achieved, and depending on the species, age,sex, physical condition, disease state, disease progression, etc., ofthe subject receiving the component. When the component is a drug, theamount administered will also depend on the drug's efficacy. In general,it would be expected that the dosage of drug required to achieve aparticular result, and delivered directly to the colon, will be lessthan the dosage required for intravenous, conventional oral or othersystemic delivery.

EXAMPLE 1 Coated Polypropylene Glycol in Dairy Cows

In this coating trial, the propylene glycol product (Glycopulp) wascoated with FOS (bioSecure™) as the coating agent. The use of propyleneglycol as a glucogenic supplement for dairy cows during the transitionphase from the middle of the dry period through the first 21 days oflactation is known. However, the addition of propylene glycol to thetotal mixed ration (TMR) is known to decrease feed intake.

The propylene glycol product (Glycopulp) was masked with a feed flavor,and coated with FOS as the coating agent. The drying agent was chicorypulp and the flavoring agent was Milk Buds™ F.S.

Glycopulp is a blend of chicory pulp (1mm screen) and feed gradepropylene glycol in a ratio of 55:45 (W/W). The Glycopulp was suppliedby Socode S.C. (Warcoing, Belgium). Chicory pulp (1 mm screen) was usedas a drying agent during the coating process. The FOS used as thecoating agent was suspended in water prior to coating.

The flavoring agent, Milk Buds™ F.S. (Lot No. 8176) was supplied byQualiTech (Chaska Minn., Product Code 2741). The flavoring agent can beadded to feed, for example, at a rate of about 0.25-4 ounces per ton offinished feed. In this trial, a rate of approximately 2 ounces per tonof finished feed was used. The flavoring agent was suspended in waterwith the FOS prior to coating.

Coating Process

Engineered Technology Systems, Inc. (ETS, Gilroy, Calif.) offers coatingequipment to the agricultural seed market sector, manufactured foodindustries and pharmaceutical industry. The approach to the ETS line ofcoating systems is the rapid application of liquid and powder materialsto create a thin film polymer coating, build-up coating or sphericalpellet. The system “coats” products by centrifugal force as the producttravels rapidly around the stator (bowl) via the movement of a rotor.The rotor is the bottom end of the equipment that moves the product bycentrifugal force. The atomizer sits slightly above the rotor. Theatomizer is a small spinning disk through which liquids are pumped viaperistaltic pumps at precise rates. When liquids hit the atomizer theliquids are atomized into small particles that are projected onto thematerials being moved around the stator. Powders can be injected intothe coating equipment at any time during the process to allow a“build-up” process to form around a nucleolus (nucleolus being theproduct coated). The equipment achieves all of these functions bycomputerized controls that monitor and provide operator feedback. Theentire coating process is a controlled semi-continuous system where aknown amount of material is coated at one time. The production rate ofeach coating run takes only seconds to achieve the desired product.

Trial 1

The proportions of components used for this trial are found in the tablebelow. Three hundred twenty grams of polyethylene glycol (Glycopulp) wasplaced into the drum of the ETS R-12 rotary coater. The moving rotor wasturned on and it was determined that the sample adequately flowed in theequipment to be coated. Thirty-two milliliters of Stock Solution A (FOSand water) was applied to the rotating Glycopulp. After applying StockSolution A, 17.5 grams of chicory pulp (1 mm screen size) was applied asa drying agent. Drying can also be achieved by low temperature air.

Trial One, No Flavor Added Item Amount Stock Solution A: BioSecure FOS11 grams Water 2 liters Glycopulp 320 grams Chicory Pulp 17.6 grams

Trial 2

The proportions of components used for this trial are found in the tablebelow. Three hundred twenty grams of Glycopulp was placed into the drumof the ETS R-12 rotary coater. The moving rotor was turned on and it wasdetermined that the sample adequately flowed in the equipment to becoated. Thirty-two milliliters of Stock Solution B (FOS, flavor agent,and water) was applied to the rotating Glycopulp. After applying StockSolution B, 17.5 grams of chicory pulp (1 mm screen size) was applied asa drying agent. Drying can also be achieved by low temperature air.

Trial Two, Flavor Added Item Amount Stock Solution B: BioSecure FOS 11grams Milk Buds 1.2 mls Water 2 liters Glycopulp 320 grams Chicory Pulp17.6 grams

The source of fructo-oligosaccharide (FOS) in bioSecure™ FOS is derivedfrom chicory roots. Chicory roots are a natural source of inulin; acarbohydrate made up of fructose polymers (fructan). The fructan cannotbe metabolized by monogastrics, which lack the enzyme inulinase.Consequently, fructan passes on to the lower intestine where it isfermented by lactic acid producing bacteria such as Bifidobacterium.Gram negative bacteria such as Escherichia coli are unable to ferment orgrow on fructan; thereby a natural selection will take place promotingbeneficial bacteria in the lower intestine.

The following analysis of bioSecure™ FOS is exemplary only. As inulinand fructo-oligosaccharide are natural products, their exact compositionwill vary from crop to crop and from year to year. Additionally, theenzymatic breakdown of inulin with inulinase can vary. Neosugars areproduced by an enzymatic reaction and can also vary in the end result.

Analysis of bioSecure ™ FOS % Item Dry Matter 95 Carbohydrate Content99.9 Ash 0.1 Carbohydrates Free Sugars 8.2 Glucose 0.7 Fructose 2.9Sucrose 4.6 DP 1-10 41.1 DP 11-20 30.0 DP 21-30 17.5 DP 31-40 7.7 DP41-50 2.6 DP 51-60 1 DP 3-20 61.8 Average DP_(n) 6.6 Average DP_(n) =The average degrees of polymerization of the product.

Specifications of bioSecure ™ FOS Analysis Specification Results DryMatter (%) 95% Minimum 97.1% Ash (% of DM) 0.5% Maximum 0.1%Carbohydrate content (% of 99.5% Minimum 99.9% DM) Free Sugars (% of DM)10% Maximum 9.1% Fiber (% of DM) 90% Minimum 90.8% Total Plate Count10,000 cfu/gm Maximum 110 cfu/gm Yeasts 20 cfu/gm Maximum <10 cfu/gmMolds 20 cfu/gm Maximum <10 cfu/gm Coliforms 0 cfu/gm  0 cfu/gm

Having described the invention, alternatives and embodiments may occurto one of skill in the art. It is intended that such modifications andequivalents shall be included within the scope of the following claims.

I claim:
 1. A composition for colon-targeted delivery comprising: a) oneor more component targeted for delivery to the colon; and b)fructo-oligosaccharide (FOS) having a degree of polymerization (dp) inthe range of 2-20 units and an average dp of 2-10; wherein said one ormore component is coated with said FOS to form a FOS coated compositionsuitable for selective delivery to the colon of a monogastric animal;and wherein said one or more component comprises one or more beneficialbacteria selected from the group consisting of: Bacillus, Bacteroides,Entercoccus, Leuconostoc, Pediococcus, Pripionibacterium, Streptococcus,and a combination thereof, wherein said beneficial bacteria is notLactobacillus or Bifidobacterium.
 2. A composition for colon-targeteddelivery comprising: a) one or more component targeted for delivery tothe colon; and b) fructo-oligosaccharide (FOS) having a degree ofpolymerization (dp) in the range of 2-20 units and an average dp of2-10; wherein said one or more component is coated with said FOS to forma FOS coated composition suitable for selective delivery to the colon ofa monogastric animal; and wherein said one or more component comprises ayeast selected from the group consisting of: Saccharomyces, Candida, ora combination thereof.
 3. The composition of claim 1, wherein said oneor component further comprises one or more amino acid selected from thegroup consisting of: arginine, glycine, lysine, methionine, taurine,threonine, tryptophan, and a combination thereof.
 4. The composition ofclaim 1, wherein said one or more component further comprises theprotein insulin.
 5. The composition of claim 1, wherein said one or morecomponent further comprises one or more nutrient selected from the groupconsisting of: bone meal, grain, egg, fat, feather meal, fish meal,plant or animal byproducts, plasma, whey, soy products, and acombination thereof.
 6. The composition of claim 1, wherein said one ormore component further comprises one or more plant extract selected fromextracts of: alfalfa, angelica, anise, basil, bay leaf, calendula,chamomile, caraway, cardamom, cloves, coriander, cumin, dandelion, dill,fennel, fenugreek, garlic, glycyrrhiza, habanero pepper, horehound,horsemint, horseradish, hyssop, gentian, ginger, ginseng, juniper, kava,lemon balm, lemon grass, licorice, marjoram, Melissa, mustard, nutmeg,nettle, onion, oregano, parsley, pepper, peppermint, raspberry,rosemary, rue, savory, spearmint, tarragon, thyme, vanilla, and acombination thereof.
 7. The composition of claim 1, wherein said one ormore component further comprises one or more herb selected from thegroup consisting of: Boneset or Feverwort (Eupatorium perfoliatum),Burdock (Arctium lappa), Coltsfoot (Tussilago farfara), Comfrey(Symphytum officinale), Devil's Claw Root (Harpagophytum procumbens),Ginkgo (Ginkgo biloba), Golden Rod (Solidago virgaurea), pot Marigold(Calencula officinalis), Meadowsweet (Filipendula ulmaria), Monk'sPepper or Chasteberry (Vitex agnus-castus), Nettle (Urtica dioicea), RedPoppy Seed (Papaver rhoeas), Raspberry leaves (Rubidus idaeus), Valerianroot (Valeriana officinalis), Vervain (Verbena officinalis), Yellow Dock(Rumex crispus), and a combination thereof.
 8. The composition of claim1, wherein said one or more component further comprises one or moremineral selected from the group consisting of: calcium, chromium,cobalt, copper, iodine, iron, magnesium, manganese, organic traceminerals, phosphorus, potassium, selenium, sodium, sulfur, zinc, and acombination thereof.
 9. The composition of claim 8, wherein said mineralis a chelated mineral is selected from the group consisting of: chelatedcopper, chelated zinc, chelated iron, chelated manganese, chelatedchromium, chelated magnesium, and a combination thereof.
 10. Thecomposition of claim 9, wherein said chelated mineral comprises saidmineral bound to carbohydrate, protein, or a combination thereof.
 11. Acomposition for colon-targeted delivery comprising: a) one or morecomponent targeted for delivery to the colon; and b)fructo-oligosaccharide (FOS) having a degree of polymerization (dp) inthe range of 2-20 units and an average dp of 2-10; wherein said one ormore component is coated with said FOS to form a FOS coated compositionsuitable for selective delivery to the colon of a monogastric animal;and wherein said one or more component comprises a mold selected fromthe group consisting of Asperigillis niger, Asperillis oryzae, and acombination thereof.
 12. The composition of claim 1, wherein said one ormore component further comprises a vitamin selected from the groupconsisting of: vitamins A, B12, C, D, E, K, betaine, biotin, choline,folic acid, inositol, niacin, pantothenic acid, pyridoxine, riboflavin,thiamine, and a combination thereof.
 13. The composition of claim 1,wherein said one or more component further comprises a drug selectedfrom the group consisting of: antibiotics, antiviral agents, anti-moldagents, bloat preventatives, coccidiostats, growth enhancers, vaccines,wormers, chemotherapy agents, anti-tumor agents, insulin, and acombination thereof.
 14. The composition of claim 1, wherein said one ormore component further comprises an antibody selected from the groupconsisting of: anti-bacterial and anti-viral antibodies, and acombination thereof.
 15. The composition of claim 1, wherein said one ormore component further comprises an enzyme selected from the groupconsisting of: cellulase, hemicellulase, amylase, phytase, ligninase,and a combination thereof.
 16. A composition for colon-targeted deliverycomprising: a) one or more component targeted for delivery to the colon;and b) fructo-oligosaccharide (FOS) having a degree of polymerization(dp) in the range of 2-20 units and an average dp of 2-10, wherein saidone or more component is coated with said FOS to form a FOS coatedcomposition suitable for selective delivery to the colon of amonogastric animal; and wherein said one or more component comprises anacid selected from the group consisting of: citric acid, lactic acid,acetic acid, and a combination thereof.
 17. The composition of claim 1,wherein said one or more component further comprises an energy-providingcompound selected from the group consisting of: glucose, sucrose,fructose, propylene glycol, glucose precursors, and a combinationthereof.
 18. The composition of claim 1, wherein said one or morecomponent further comprises an unpalatable component selected from thegroup consisting of: ammonium chloride, calcium sulphate, magnesiumchloride, and a combination thereof.
 19. The composition of claim 1,wherein said one or more component, further comprises an immunestimulator selected from the group consisting of:mannose-oligosaccharide, beta-glucan, and a combination thereof.
 20. Thecomposition of claim 1, wherein said one or more component furthercomprises a spice, an essential oil, or a combination thereof.
 21. Thecomposition of claim 1, wherein said one or more component furthercomprises one or more unpalatable component selected from ammoniumchloride, calcium sulphate, magnesium chloride, propylene glycol, drugs,vitamins, and a combination thereof.
 22. The composition of claim 2,wherein said one or more component further comprises one or more vitaminselected from vitamins A, B12, C, D, E, K, betaine, biotin, choline,folic acid, inositol, niacin, pantothenic acid, pyridoxine, riboflavin,thiamine, and a combination thereof.
 23. The composition of claim 2,wherein said one or more component further comprises one or moreantibody selected from an anti-bacterial antibody, an anti-viralantibody, and a combination thereof.
 24. The composition of claim 2,wherein said one or more component further comprises one or more aminoacid selected from arginine, glycine, lysine, methionine, taurine,threonine, tryptophan, and a combination thereof.
 25. The composition ofclaim 2, wherein said one or more component further comprises one ormore enzyme selected from cellulase, hemicellulase, amylase, phytase,ligninase, and a combination thereof.
 26. The composition of claim 1,wherein said one or more component further comprises a spice, anessential oil, an immune stimulator, a plant extract, an enzyme, or acombination thereof.
 27. The composition of claim 2, wherein said one ormore component further comprises one or more of a spice, an essentialoil, an immune stimulator, a plant extract, an enzyme, or a combinationthereof.
 28. The composition of claim 11, wherein said one or morecomponent further comprises one or more of a spice, an essential oil, animmune stimulator, a plant extract, an enzyme, or a combination thereof.29. The composition of claim 16, wherein said one or more componentfurther comprises one or more of a spice, an essential oil, an immunestimulator, a plant extract, an enzyme, or a combination thereof.
 30. Amethod for delivering one or more component to the colon of amonogastric animal, said method comprising administering to the animalthe composition of claim
 1. 31. A method for delivering one or morecomponent to the colon of a monogastric animal, said method comprisingadministering to the animal the composition of claim
 2. 32. A method fordelivering one or more component to the colon of a monogastric animal,said method comprising administering to the animal the composition ofclaim
 11. 33. A method for delivering one or more component to the colonof a monogastric animal, said method comprising administering to theanimal the composition of claim
 16. 34. A method for delivering one ormore component to the colon of a monogastric animal, said methodcomprising administering to the animal the composition of claim
 21. 35.A method for delivering one or more component to the colon of amonogastric animal, said method comprising administering to the animalthe composition of claim
 22. 36. A method for delivering one or morecomponent to the colon of a monogastric animal, said method comprisingadministering to the animal the composition of claim
 23. 37. A methodfor delivering one or more component to the colon of a monogastricanimal, said method comprising administering to the animal thecomposition of claim
 24. 38. A method for delivering one or morecomponent to the colon of a monogastric animal, said method comprisingadministering to the animal the composition of claim 25.